Department of Tropical Medicine, Army Medical University, Chongqing, China.
Sci Rep. 2021 Jun 25;11(1):13345. doi: 10.1038/s41598-021-92906-5.
No FDA approved pharmacological therapy is available to reduce neuroinflammation following heatstroke. Previous studies have indicated that dexmedetomidine (DEX) could protect against inflammation and brain injury in various inflammation-associated diseases. However, no one has tested whether DEX has neuro-protective effects in heatstroke. In this study, we focused on microglial phenotypic modulation to investigate the mechanisms underlying the anti-inflammatory effects of DEX in vivo and in vitro. We found that DEX treatment reduced the expression of CD68, iNOS, TNF-α, and IL-1β, and increased the expression of CD206, Arg1, IL-10 and TGF-β in microglia, ameliorating heatstroke induced neuroinflammation and brain injury in mice. TREM2, whose neuro-protective function has been validated by genetic studies in Alzheimer's disease and Nasu-Hakola disease, was significantly promoted by DEX in the microglia. TREM2 esiRNA reversed the DEX-induced activation of PI3K/Akt signalling. Overall these findings indicated that DEX may serve, as a potential therapeutic approach to ameliorate heatstroke induced neuroinflammation and brain injury via TREM2 by activating PI3K/Akt signalling.
目前尚无经美国食品药品监督管理局批准的药理学疗法可用于减轻中暑后的神经炎症。先前的研究表明，右美托咪定（DEX）可预防各种炎症相关疾病中的炎症和脑损伤。然而，尚未有人测试 DEX 是否对中暑具有神经保护作用。在这项研究中，我们专注于小胶质细胞表型调节，以研究 DEX 在体内和体外发挥抗炎作用的机制。我们发现，DEX 治疗可降低小胶质细胞中 CD68、iNOS、TNF-α 和 IL-1β 的表达，并增加 CD206、Arg1、IL-10 和 TGF-β 的表达，从而改善中暑诱导的小鼠神经炎症和脑损伤。TREM2 的神经保护功能已在阿尔茨海默病和 Nasu-Hakola 病的遗传研究中得到验证，DEX 可显著促进小胶质细胞中 TREM2 的表达。TREM2 esiRNA 逆转了 DEX 诱导的 PI3K/Akt 信号通路的激活。总的来说，这些发现表明，DEX 可能通过激活 PI3K/Akt 信号通路，通过 TREM2 作为一种潜在的治疗方法来改善中暑引起的神经炎症和脑损伤。
